Department of Biomedical Sciences, Cellular Biochemistry, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk-Antwerpen, Belgium.
Purinergic Signal. 2006 Sep;2(3):451-69. doi: 10.1007/s11302-006-9008-0. Epub 2006 Jun 7.
The role of nucleotides in intracellular energy provision and nucleic acid synthesis has been known for a long time. In the past decade, evidence has been presented that, in addition to these functions, nucleotides are also autocrine and paracrine messenger molecules that initiate and regulate a large number of biological processes. The actions of extracellular nucleotides are mediated by ionotropic P2X and metabotropic P2Y receptors, while hydrolysis by ecto-enzymes modulates the initial signal. An increasing number of studies have been performed to obtain information on the signal transduction pathways activated by nucleotide receptors. The development of specific and stable purinergic receptor agonists and antagonists with therapeutical potential largely contributed to the identification of receptors responsible for nucleotide-activated pathways. This article reviews the signal transduction pathways activated by P2Y receptors, the involved second messenger systems, GTPases and protein kinases, as well as recent findings concerning P2Y receptor signalling in C6 glioma cells. Besides vertical signal transduction, lateral cross-talks with pathways activated by other G protein-coupled receptors and growth factor receptors are discussed.
核苷酸在细胞内能量供应和核酸合成中的作用早已为人所知。在过去的十年中，有证据表明，除了这些功能外，核苷酸还是内分泌和旁分泌的信使分子，能够启动和调节大量的生物过程。细胞外核苷酸的作用是通过离子型 P2X 和代谢型 P2Y 受体介导的，而外切酶的水解则调节初始信号。越来越多的研究旨在获取关于核苷酸受体激活的信号转导途径的信息。具有治疗潜力的特异性和稳定的嘌呤能受体激动剂和拮抗剂的开发在很大程度上有助于确定负责核苷酸激活途径的受体。本文综述了 P2Y 受体激活的信号转导途径，涉及的第二信使系统、G 蛋白和蛋白激酶，以及最近关于 C6 神经胶质瘤细胞中 P2Y 受体信号的发现。除了纵向信号转导，还讨论了与其他 G 蛋白偶联受体和生长因子受体激活的途径的横向交叉对话。
